Proper functioning of the salivary glands is essential to oral health. In recent years the number of hormones and neurotransmitters known to have important physiological roles in regulating salivary gland function has markedly increased. With this increase has come an appreciation that various disease states affecting salivary processes may involve one or more of these compounds. One of the primary examples of "new" agents that are intimately involved in gland function is vasoactive intestinal peptide (VIP). This 28 amino acid peptide is the primary candidate for the agent causing the atropine-resistant vasodilation seen in submandibular glands of several species. Experimental evidence suggests other functions of VIP in salivary glands. The objective of the proposed research is to characterize the cell surface receptors for VIP in rat submandibular gland. A second objective is to explore the interaction of receptors for distinct neurotransmitters in terms of their crossmodulation of receptor affinity and density. Our approach to these objectives will involve first, studies of the effects of VIP and related peptides in isolated, perfused submandibular glands in terms of blood flow, salivary secretion and saliva electrolyte and protein content. Second, we will examine isolated acinar cells for peptide effects on ion fluxes. Third, these same preparations will be assayed for responsiveness of intracellular messengers to VIP. Finally, we will use radioligand binding studies to (1) correlate these functional studies with the interaction of VIP and its receptor and (2) examine the phenomenon of receptor cross-talk. The HT29 cell line of colonic origin has many attributes that make it a useful model system for studying many of the above processes and will be used secondarily in our studies of VIP effects on submandibular gland function. Attainment of these objectives will provide a fuller understanding of normal salivary function and suggest new avenues of investigation in disease states affecting exocrine glands.